Autoinjector with an inner plunger which disengages the outer plunger to retract the syringe carrier

ABSTRACT

Described is an autoinjector comprising a case, a chassis slidably arranged in the case, a syringe carrier operably coupled to the chassis, an outer plunger selectively engaged to the chassis, an inner plunger selectively engaged to the outer plunger, and a drive spring applying a biasing force to the outer plunger. The biasing force is applied to the inner plunger when the inner plunger is engaged to the outer plunger. Rotation of the chassis causes the inner plunger to rotate relative to the outer plunger and disengage the outer plunger to remove the biasing force from the drive spring on the inner plunger. When the inner plunger disengages the outer plunger, the biasing force of the drive spring pushes the chassis to retract the syringe carrier relative to the case.

CROSS REFERENCE TO RELATED APPLICATIONS

The present application is a continuation of U.S. patent applicationSer. No. 15/821,166, filed Nov. 22, 2017, which is a continuation ofU.S. patent application Ser. No. 14/366,868, filed Jun. 19, 2014, nowU.S. Pat. No. 9,827,381, which is a U.S. National Phase Applicationpursuant to 35 U.S.C. § 371 of International Application No.PCT/EP2012/076097, filed Dec. 19, 2012, which claims priority toEuropean Patent Application No. 11194775.0, filed Dec. 21, 2011. Theentire disclosure contents of these applications are herewithincorporated by reference into the present application.

TECHNICAL FIELD

The invention relates to an autoinjector for administering a medicament.

BACKGROUND

Administering an injection is a process which presents a number of risksand challenges for users and healthcare professionals, both mental andphysical injection devices typically fall into two categories—manualdevices and autoinjectors. In a conventional manual device, a user mustprovide force to drive a medicament through a needle. This is typicallydone by some form of button/plunger that has to be continuously pressedduring the injection. There are numerous disadvantages for the user fromthis approach. For example, if the user stops pressing thebutton/plunger, the injection will stop and may not deliver an intendeddose to a patient. Further, the force required to push thebutton/plunger may be too high for the user (e.g., if the user iselderly). And, aligning the injection device, administering theinjection and keeping the injection device still during the injectionmay require dexterity which some patients (e.g., elderly patients,children, arthritic patients, etc.) may not have.

Autoinjector devices aim to make self-injection easier for patients. Aconventional autoinjector may provide the force for administering theinjection by a spring, and trigger button or other mechanism may be usedto activate the injection. Autoinjectors may be single-use or reusabledevices.

There remains a need for an improved autoinjector.

SUMMARY

It is an object of the present invention to provide an improvedautoinjector.

In an exemplary embodiment, an autoinjector according to the presentinvention comprises a case, a chassis slidably arranged in the case, asyringe carrier operably coupled to the chassis, an outer plungerselectively engaged to the chassis, an inner plunger selectively engagedto the outer plunger, and a drive spring applying a biasing force to theouter plunger. The biasing force is applied to the inner plunger whenthe inner plunger is engaged to the outer plunger. Rotation of thechassis causes the inner plunger to rotate relative to the outer plungerand disengage the outer plunger to remove the biasing force from thedrive spring on the inner plunger. When the inner plunger disengages theouter plunger, the biasing force of the drive spring pushes the chassisto retract the syringe carrier relative to the case.

In an exemplary embodiment, the autoinjector further comprises a needleshroud slidably arranged in the case. Axial movement of the needleshroud relative to the case causes rotation of the chassis relative tothe needle shroud.

In an exemplary embodiment, the autoinjector further comprises a firingnut rotatably disposed on the chassis. The firing nut engages the outerplunger when in a first angular position and disengages the outerplunger when in a second angular position. The case includes a stemadapted to rotate the firing nut from the first angular position to thesecond angular position. When the firing nut is in the second angularposition, the biasing force of the drive spring pushes the outer plungerin a distal direction (D) relative to the case.

In an exemplary embodiment, the needle shroud includes a guide trackadapted to engage a pin on the chassis. The pin moves from an angledportion to an axial portion of the guide track causing rotation of thechassis relative to the needle shroud when the needle shroud translatesrelative to the case.

In an exemplary embodiment, the autoinjector further comprises acoupling carrier coupled to the syringe carrier and selectively engagedto the inner plunger. The coupling carrier includes resilient armsadapted to releasably engage the inner plunger, and the biasing force ofthe drive spring causes the inner plunger to deflect the resilient armswhen a front stop on the syringe carrier abuts a shroud shoulder on theneedle shroud. When the resilient arms disengage the inner plunger, theinner plunger is adapted to push a stopper in a syringe. The chassisincludes a resilient clip adapted to engage a stop on the couplingcarrier. When the biasing force of the drive spring pushes the chassis,the clip engages the stop and retracts the coupling carrier and thesyringe carrier relative to the case.

In an exemplary embodiment, the autoinjector further comprises a controlspring axially biasing the needle shroud relative to the case.

In an exemplary embodiment, rotation of the chassis relative to theneedle shroud causes rotation of the firing nut to a third angularposition in which the firing nut is adapted to advance over the stem.

In an exemplary embodiment, the needle shroud includes a resilientnon-return clip adapted to engage the case and prevent translation ofthe needle shroud relative to the case.

Further scope of applicability of the present invention will becomeapparent from the detailed description given hereinafter. However, itshould be understood that the detailed description and specificexamples, while indicating preferred embodiments of the invention, aregiven by way of illustration only, since various changes andmodifications within the spirit and scope of the invention will becomeapparent to those skilled in the art from this detailed description.

BRIEF DESCRIPTION OF THE DRAWINGS

The present invention will become more fully understood from thedetailed description given hereinbelow and the accompanying drawingswhich are given by way of illustration only, and thus, are not limitiveof the present invention, and wherein:

FIGS. 1A and 1B show two longitudinal sections of an exemplaryembodiment of an autoinjector in an initial state according to thepresent invention,

FIG. 2 is a perspective view of exemplary embodiments of a syringe, aninner plunger and an outer plunger for an autoinjector according to thepresent invention,

FIG. 3 is a perspective view of an exemplary embodiment of an outerplunger guided in a needle shroud according to the present invention,

FIGS. 4A and 4B show two longitudinal sections of an exemplaryembodiment of an autoinjector with a distal end pushed against aninjection site according to the present invention,

FIGS. 5A and 5B show two longitudinal sections of an exemplaryembodiment of an autoinjector with a distal end pushed against aninjection site according to the present invention,

FIGS. 6A and 6B show two longitudinal sections of an exemplaryembodiment of an autoinjector with an injection needle extended beyondthe distal end according to the present invention,

FIG. 7 is a perspective view of exemplary embodiments of internalcomponents of an exemplary embodiment of an autoinjector with a needleextended according to the present invention,

FIGS. 8A and 8B show two longitudinal sections of an exemplaryembodiment of an autoinjector after an injection according to thepresent invention,

FIGS. 9A and 9B show two longitudinal sections of an exemplaryembodiment of an autoinjector removed from an injection site accordingto the present invention, and

FIGS. 10A and 10B show two longitudinal sections of an exemplaryembodiment of an autoinjector removed from an injection site accordingto the present invention.

Corresponding parts are marked with the same reference symbols in allfigures.

DETAILED DESCRIPTION

FIGS. 1A and 1B show two longitudinal sections of an exemplaryembodiment of an autoinjector 1 for delivering a medicament. Thesectional planes of the longitudinal sections are essentially orientedperpendicularly with respect to each other.

In an exemplary embodiment, the autoinjector 1 comprises an elongatecase 2 comprising a rear case 2.1 coupled to a front case 2.2. A needleshroud 3 is telescopically arranged on the case 2 and may be resilientlycoupled to the front case 2.2 by a control spring 10 which applies abiasing force on the needle shroud 3 toward a distal direction D.

A syringe carrier 4 is slidably disposed in the case 2 and is arrangedto hold a syringe 5 having a needle 15. As explained further below, thesyringe carrier 4 includes an abutment surface 4.1 formed on its distalend that is adapted to abut a shoulder 3.4 formed on the distal portionof the needle shroud 3 when the syringe carrier 4 is moving axially inthe distal direction D relative to the needle shroud 3. A distancebetween a distal face of the needle shroud 3 and the shoulder 3.4 maydefine the injection depth of the needle 15.

A proximal end of the needle shroud 3 is adapted to abut a chassis 8which is slidably disposed in the case 2. A collar 8.1 disposed on aproximal end of the chassis 8 acts as a proximal bearing for a drivespring 6, which bears distally on a shoulder 7.1 on an outer plunger 7that is telescopically arranged on the chassis 8.

As shown in FIG. 7, in an exemplary embodiment, the collar 8.1 includesa radial protrusion 8.4 which is adapted to prevent rotation of thechassis 8 relative to the rear case 2.1 when the autoinjector 1 ispressed against an injection site. In an exemplary embodiment, theradial protrusion 8.4 is adapted to engage a channel formed in the rearcase 2.1, and when the needle shroud 3 is pressed against the injectionsite, the radial protrusion 8.4 abuts the channel and is prevented fromrotating relative to the rear case 2.1. Prior to and after use, theradial protrusion 8.4 does not abut the channel and thus the collar 8.1(and chassis 8) may rotate relative to the rear case 2.1.

Referring back to FIGS. 1A and 1B, in an exemplary embodiment, a firingnut 17 is selectively engaged to outer plunger 7. The firing nut 17 mayrotatably sit in a cavity of the collar 8.1. The firing nut 17 mayinclude teeth 17.1 which are adapted to engage teeth 7.2 formed on asurface of the outer plunger 7. The teeth 17.1 on the firing nut 17 maybe formed on a selected portion of the firing nut 17, such that rotationof the firing nut 17 relative to the outer plunger 7 from a firstangular position to a second angular position may disengage the outerplunger from the firing nut 17.

The teeth 7.2 of the outer plunger 7 may also engage corresponding teeth12.1 formed on an inner plunger 12. For example, the inner plunger 12may include a stem and a transverse element coupled to a proximalportion of the stem, and an outer surface of the transverse element mayinclude the teeth 12.1 for engaging the teeth 7.2 on the outer plunger7.

As shown in FIG. 3, the outer plunger 7 may be keyed to the needleshroud 3 to allow axial relative movement but prevent rotationalrelative movement. For example, the outer plunger 7 may include aplurality of legs, and one or more of the legs may be adapted to engagea groove or channel formed in the needle shroud 3.

Referring back to FIGS. 1A and 1B, a coupling carrier 11 is slidablyarranged in and keyed to the chassis 8 (allowing for relativetranslation and joint rotation) and is coupled to the syringe carrier 4.The inner plunger 12 is arranged telescopically in the coupling carrier11 to allow for axial movement of the inner plunger 12 relative to thecoupling carrier 11 and joint rotation with the coupling carrier 11relative to the chassis 8. Two resilient arms 11.1 on the couplingcarrier 11 are arranged to selectively engage a groove between a firstplunger shoulder 12.2 and a second plunger shoulder 12.4 on the innerplunger 12 in a manner to couple the inner plunger 12 and the couplingcarrier 11 for joint axial translation. In an exemplary embodiment, theresilient arms 11.1 and the first plunger shoulder 12.2 are in a rampedengagement so as to allow the resilient arms 11.1 to deflect radiallyand disengage the inner plunger 12.

In an exemplary embodiment, the resilient arms 11.1 are maintained inengagement with the first plunger shoulder 12.2, because the needleshroud 3 abuts the resilient arms 11.1. However, the needle shroud 3includes first apertures 3.2 which, when aligned with the resilient arms11.1, allow space for the resilient arms 11.1 to deflect radially anddisengage the inner plunger 12.

In an exemplary embodiment, a proximal end of the case 2 includes a stem2.7 extending in the proximal direction and having a thread adapted toengage a corresponding thread 17.2 formed in the firing nut 17. Asexplained further below, when the thread on the stem 2.7 engages thethread 17.2 on the firing nut 17, the firing nut 17 rotates relative tothe outer plunger 7.

In an exemplary embodiment, a cap (not shown) is removably coupled tothe front case 2.2 and/or the needle shroud 3. The cap may be coupled toa needle sheath (not illustrated) arranged on the needle 15, and removalof the cap may remove the needle sheath.

FIGS. 1A and 1B show the autoinjector 1 in an initial state, prior touse. Prior to use, the needle shroud 3 extends from the case 2 under thebiasing force of the control spring 10 to cover a distal tip of theneedle 15. As shown in FIG. 7, in an exemplary embodiment, the needleshroud 3 includes a guide track 14 having an axial portion 14.1 and anangled portion 14.2, and a pin 8.2 on the chassis 8 engages the guidetrack 14. In the initial state, the pin 8.2 is in a distal portion ofthe angled section 14.2. Referring back to FIGS. 1A and 1B, the firingnut 17 and the inner plunger 12 are both engaged to the outer plunger 7,and the coupling carrier 11 is engaged to the inner plunger 12.

As shown in FIGS. 4A and 4B, when the autoinjector 1 is pressed againstan injection site, the needle shroud 3 translates into the case 2 in theproximal direction P, compressing the control spring 10. The needleshroud 3 pushes the chassis 8 in the proximal direction P. Movement ofthe chassis 8 results in corresponding movement of the firing nut 17which also results in corresponding movement of the outer plunger 7,since the firing nut 17 is engaged to the outer plunger 7 via teeth17.1. Since the inner plunger 12 is engaged to the outer plunger 7, theinner plunger 12 and the coupling carrier 11, the syringe carrier 4 andthe syringe 5 move in conjunction with the inner plunger 12.

As shown in FIGS. 5A and 5B, the autoinjector 1 is pressed furtheragainst the injection site (substantially fully compressing the controlspring 10), and the stem 2.7 engages the firing nut 17. As the stem 2.7engages the firing nut 17, the firing nut 17 rotates from the firstangular position to the second angular position, disengaging the outerplunger 7.

As shown in FIGS. 6A and 6B, when the firing nut 17 rotates into thesecond angular position, the outer plunger 7 is released from thechassis 8, and the drive spring 6 pushes the outer plunger 7 in thedistal direction D. Because the inner plunger 12 is coupled to the outerplunger 7, the inner plunger 12 (and the coupling carrier 11, syringecarrier 4 and syringe 5) moves in the distal direction D. Movement ofthe syringe carrier 4 in the distal direction D leads to insertion ofthe needle 15 in the injection site. A penetration depth of the needle15 is defined by a front stop 4.1 on the syringe carrier 4 abutting aninner distal shroud shoulder 3.4 on the needle shroud 3.

As shown in FIGS. 8A and 8B, when the front stop 4.1 on the syringecarrier 4 abuts the inner distal shroud shoulder 3.4 on the needleshroud 3, the resilient arms 11.1 of the coupling carrier 11 align withthe first apertures 3.2 of the needle shroud 3, and the force of thedrive spring 6 causes the first plunger shoulder 12.2 to deflect theresilient arms 11.1 of the coupling carrier 11 into the first apertures3.2. When the resilient arms 11.1 are deflected, the inner plunger 12moves in the distal direction D relative to the coupling carrier 11. Theinner plunger 12 abuts a stopper 13 in the syringe 5 and pushes thestopper 13 in the distal direction D to expel the medicament from theneedle 15.

As shown in FIGS. 9A and 9B, when the autoinjector 1 is removed from theinjection site after an injection is complete or during the injection,the biasing force of the control spring 10 causes the needle shroud 3 totranslate in the distal direction D relative to the case 2. Under theforce of the drive spring 6, the outer plunger 7 translates in thedistal direction D relative to the case 2. As the needle shroud 3translates in the distal direction D relative to the case 2, theengagement of the pin 8.2 on the chassis 8 and the guide track 14 causesthe chassis 8 to rotate relative to the case 2. As the needle shroud 3translates, the geometry of the guide track 14 causes the pin 8.2 tomove through the angled portion 14.2 of the guide track 14 causingrotation of the chassis 8 relative to the needle shroud 3 and into theaxial portion 14.1 of the guide track 14 which allows for axial movementof the needle shroud 3 relative to the chassis 8. Because the outerplunger 7 is keyed to the needle shroud 3, the chassis 8 rotatesrelative to the outer plunger 7 and causes rotation of the couplingcarrier 11 which, in turn, rotates the inner plunger 12 to disengagefrom the outer plunger 7. Thus, the teeth 12.1 on the inner plunger 12disengage the teeth 7.2 on the outer plunger 7. Further, extension ofthe needle shroud 3 relative to the case 2 is limited by the pin 8.2abutting the proximal end of the axial portion 14.1 of the guide track14 during translation of the needle shroud 3.

When the inner plunger 12 disengages the outer plunger 7, the force ofthe drive spring 6 does not act on the inner plunger 12. Thus, even ifthe autoinjector 1 is removed from the injection site during theinjection, the expulsion of the medicament from the syringe 5 will stop,because there is no force to move the inner plunger 12 (and the stopper13).

As the insertion depth of the needle 15 is defined by the syringecarrier 4 contacting the needle shroud 3, allowing the needle shroud 3to re-advance on removal from the injection site could also allow thesyringe 5 to advance further. In order to avoid this, one or moreresilient clips 8.5 are arranged on the chassis 8 to engage a stop 11.2on the coupling carrier 11 at the end of the rotation of the chassis 8.The clips 8.5 prevents the coupling carrier 11 (and the syringe carrier4 coupled thereto and the syringe 5) from advancing in the distaldirection D after the autoinjector 1 has been removed from the injectionsite.

FIGS. 10A and 10B show the needle shroud 3 in its extended state and thesyringe carrier 4 (and the syringe 5) in a retracted state. In anexemplary embodiment, when the chassis 8 rotates by movement of theguide pin 8.2 in the guide track 14, the firing nut 17 rotates to athird angular position and disengages the thread on the stem 2.7 (whichwas preventing movement of the firing nut 17 in the proximal direction Prelative to the stem 2.7), allowing the firing nut 17 and the collar 8.1to be pushed in the proximal direction P against the proximal end of thecase 2 under the force of the drive spring 6. In another exemplaryembodiment, the force of the drive spring 6 pushes the collar 8.1 in theproximal direction P causing the firing nut 17 to rotate to the thirdangular position and disengages the thread on the stem 2.7 (or,alternatively, follows the thread on the stem 2.7 until it abuts theproximal end of the case). The proximal movement of the collar 8.1causes a proximal movement of the chassis 8, the coupling carrier 11 andthe syringe carrier 4, which retracts the syringe 5 and the needle 15 inthe proximal direction P relative to the case 2. For example, the stop11.2 on the coupling carrier 11 may engage the clip 8.5 on the chassis8, such that the proximal movement of the chassis 8 may result in acorresponding proximal movement of the coupling carrier 11. The residualforce in the drive spring 6 may maintain the syringe 5 in a retractedposition relative to the case 5.

Hooks 3.6 on a distal end of the needle shroud 3 may engage a distalcase shoulder 2.4 to limit extension of the needle shroud 3 relative tothe case 2 under the force of the control spring 10.

In an exemplary embodiment, a resilient non-return clip (not shown) maybe arranged on the needle shroud 3 and adapted to engage the case 2after the needle shroud 3 has been extended.

The non-return clip may prevent the needle shroud 3 from moving in theproximal direction P relative to the case 2 if the autoinjector 1 ispressed against a subsequent injection site or during handling after aninjection.

In an exemplary embodiment, a viewing window 16 is arranged in the case2 for inspecting contents of the syringe 5.

The term “drug” or “medicament”, as used herein, means a pharmaceuticalformulation containing at least one pharmaceutically active compound,

wherein in one embodiment the pharmaceutically active compound has amolecular weight up to 1500 Da and/or is a peptide, a proteine, apolysaccharide, a vaccine, a DNA, a RNA, an enzyme, an antibody or afragment thereof, a hormone or an oligonucleotide, or a mixture of theabove-mentioned pharmaceutically active compound,

wherein in a further embodiment the pharmaceutically active compound isuseful for the treatment and/or prophylaxis of diabetes mellitus orcomplications associated with diabetes mellitus such as diabeticretinopathy, thromboembolism disorders such as deep vein or pulmonarythromboembolism, acute coronary syndrome (ACS), angina, myocardialinfarction, cancer, macular degeneration, inflammation, hay fever,atherosclerosis and/or rheumatoid arthritis,

wherein in a further embodiment the pharmaceutically active compoundcomprises at least one peptide for the treatment and/or prophylaxis ofdiabetes mellitus or complications associated with diabetes mellitussuch as diabetic retinopathy,

wherein in a further embodiment the pharmaceutically active compoundcomprises at least one human insulin or a human insulin analogue orderivative, glucagon-like peptide (GLP-1) or an analogue or derivativethereof, or exendin-3 or exendin-4 or an analogue or derivative ofexendin-3 or exendin-4.

Insulin analogues are for example Gly(A21), Arg(B31), Arg(B32) humaninsulin; Lys(B3), Glu(B29) human insulin; Lys(B28), Pro(B29) humaninsulin; Asp(B28) human insulin; human insulin, wherein proline inposition B28 is replaced by Asp, Lys, Leu, Val or Ala and wherein inposition B29 Lys may be replaced by Pro; Ala(B26) human insulin;Des(B28-B30) human insulin; Des(B27) human insulin and Des(B30) humaninsulin.

Insulin derivates are for example B29-N-myristoyl-des(B30) humaninsulin; B29-N-palmitoyl-des(B30) human insulin; B29-N-myristoyl humaninsulin; B29-N-palmitoyl human insulin; B28-N-myristoyl LysB28ProB29human insulin; B28-N-palmitoyl-LysB28ProB29 human insulin;B30-N-myristoyl-ThrB29LysB30 human insulin; B30-N-palmitoyl-ThrB29LysB30human insulin; B29-N—(N-palmitoyl-Y-glutamyl)-des(B30) human insulin;B29-N—(N-lithocholyl-Y-glutamyl)-des(B30) human insulin;B29-N-(ω-carboxyheptadecanoyl)-des(B30) human insulin andB29-N-(ω-carboxyheptadecanoyl) human insulin.

Exendin-4 for example means Exendin-4(1-39), a peptide of the sequenceH-His-Gly-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Leu-Ser-Lys-Gln-Met-Glu-Glu-Glu-Ala-Val-Arg-Leu-Phe-Ile-Glu-Trp-Leu-Lys-Asn-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH2.

Exendin-4 derivatives are for example selected from the following listof compounds:

H-(Lys)4-des Pro36, des Pro37 Exendin-4(1-39)-NH2, H-(Lys)5-des Pro36,des Pro37 Exendin-4(1-39)-NH2, des Pro36 Exendin-4(1-39), des Pro36[Asp28] Exendin-4(1-39), des Pro36 [IsoAsp28] Exendin-4(1-39), des Pro36[Met(O)14, Asp28] Exendin-4(1-39), des Pro36 [Met(O)14, IsoAsp28]Exendin-4(1-39), des Pro36 [Trp(O2)25, Asp28] Exendin-4(1-39), des Pro36[Trp(O2)25, IsoAsp28] Exendin-4(1-39), des Pro36 [Met(O)14 Trp(O2)25,Asp28] Exendin-4(1-39), des Pro36 [Met(O)14 Trp(O2)25, IsoAsp28]Exendin-4(1-39); or des Pro36 [Asp28] Exendin-4(1-39), des Pro36[IsoAsp28] Exendin-4(1-39), des Pro36 [Met(O)14, Asp28] Exendin-4(1-39),des Pro36 [Met(O)14, IsoAsp28] Exendin-4(1-39), des Pro36 [Trp(O2)25,Asp28] Exendin-4(1-39), des Pro36 [Trp(O2)25, IsoAsp28] Exendin-4(1-39),des Pro36 [Met(O)14 Trp(O2)25, Asp28] Exendin-4(1-39), des Pro36[Met(O)14 Trp(O2)25, IsoAsp28] Exendin-4(1-39),

wherein the group -Lys6-NH2 may be bound to the C-terminus of theExendin-4 derivative;or an Exendin-4 derivative of the sequence

des Pro36 Exendin-4(1-39)-Lys6-NH2 (AVE0010), H-(Lys)6-des Pro36 [Asp28]Exendin-4(1-39)-Lys6-NH2, des Asp28 Pro36, Pro37,Pro38Exendin-4(1-39)-NH2, H-(Lys)6-des Pro36, Pro38 [Asp28]Exendin-4(1-39)-NH2, H-Asn-(Glu)5des Pro36, Pro37, Pro38 [Asp28]Exendin-4(1-39)-NH2, des Pro36, Pro37, Pro38 [Asp28]Exendin-4(1-39)-(Lys)6-NH2, H-(Lys)6-des Pro36, Pro37, Pro38 [Asp28]Exendin-4(1-39)-(Lys)6-NH2, H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Asp28]Exendin-4(1-39)-(Lys)6-NH2, H-(Lys)6-des Pro36 [Trp(O2)25, Asp28]Exendin-4(1-39)-Lys6-NH2, H-des Asp28 Pro36, Pro37, Pro38 [Trp(O2)25]Exendin-4(1-39)-NH2, H-(Lys)6-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28]Exendin-4(1-39)-NH2, H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Trp(O2)25,Asp28] Exendin-4(1-39)-NH2, des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28]Exendin-4(1-39)-(Lys)6-NH2, H-(Lys)6-des Pro36, Pro37, Pro38 [Trp(O2)25,Asp28] Exendin-4(1-39)-(Lys)6-NH2, H-Asn-(Glu)5-des Pro36, Pro37, Pro38[Trp(O2)25, Asp28] Exendin-4(1-39)-(Lys)6-NH2, H-(Lys)6-des Pro36[Met(O)14, Asp28] Exendin-4(1-39)-Lys6-NH2, des Met(O)14 Asp28 Pro36,Pro37, Pro38 Exendin-4(1-39)-NH2, H-(Lys)6-desPro36, Pro37, Pro38[Met(O)14, Asp28] Exendin-4(1-39)-NH2, H-Asn-(Glu)5-des Pro36, Pro37,Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-NH2, des Pro36, Pro37, Pro38[Met(O)14, Asp28] Exendin-4(1-39)-(Lys)6-NH2, H-(Lys)6-des Pro36, Pro37,Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-(Lys)6-NH2, H-Asn-(Glu)5 desPro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-(Lys)6-NH2,H-Lys6-des Pro36 [Met(O)14, Trp(O2)25, Asp28] Exendin-4(1-39)-Lys6-NH2,H-des Asp28 Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25]Exendin-4(1-39)-NH2, H-(Lys)6-des Pro36, Pro37, Pro38 [Met(O)14, Asp28]Exendin-4(1-39)-NH2, H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Met(O)14,Trp(O2)25, Asp28] Exendin-4(1-39)-NH2, des Pro36, Pro37, Pro38[Met(O)14, Trp(O2)25, Asp28] Exendin-4(1-39)-(Lys)6-NH2, H-(Lys)6-desPro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28]Exendin-4(S1-39)-(Lys)6-NH2, H-Asn-(Glu)5-des Pro36, Pro37, Pro38[Met(O)14, Trp(O2)25, Asp28] Exendin-4(1-39)-(Lys)6-NH2;

or a pharmaceutically acceptable salt or solvate of any one of theafore-mentioned Exendin-4 derivative.

Hormones are for example hypophysis hormones or hypothalamus hormones orregulatory active peptides and their antagonists as listed in RoteListe, ed. 2008, Chapter 50, such as Gonadotropine (Follitropin,Lutropin, Choriongonadotropin, Menotropin), Somatropine (Somatropin),Desmopressin, Terlipressin, Gonadorelin, Triptorelin, Leuprorelin,Buserelin, Nafarelin, Goserelin.

A polysaccharide is for example a glucosaminoglycane, a hyaluronic acid,a heparin, a low molecular weight heparin or an ultra low molecularweight heparin or a derivative thereof, or a sulphated, e.g. apoly-sulphated form of the above-mentioned polysaccharides, and/or apharmaceutically acceptable salt thereof. An example of apharmaceutically acceptable salt of a poly-sulphated low molecularweight heparin is enoxaparin sodium.

Antibodies are globular plasma proteins (˜150 kDa) that are also knownas immunoglobulins which share a basic structure. As they have sugarchains added to amino acid residues, they are glycoproteins. The basicfunctional unit of each antibody is an immunoglobulin (Ig) monomer(containing only one Ig unit); secreted antibodies can also be dimericwith two Ig units as with IgA, tetrameric with four Ig units liketeleost fish IgM, or pentameric with five Ig units, like mammalian IgM.

The Ig monomer is a “Y”-shaped molecule that consists of fourpolypeptide chains; two identical heavy chains and two identical lightchains connected by disulfide bonds between cysteine residues. Eachheavy chain is about 440 amino acids long; each light chain is about 220amino acids long. Heavy and light chains each contain intrachaindisulfide bonds which stabilize their folding. Each chain is composed ofstructural domains called Ig domains. These domains contain about 70-110amino acids and are classified into different categories (for example,variable or V, and constant or C) according to their size and function.They have a characteristic immunoglobulin fold in which two β sheetscreate a “sandwich” shape, held together by interactions betweenconserved cysteines and other charged amino acids.

There are five types of mammalian Ig heavy chain denoted by α, δ, ε, γ,and μ. The type of heavy chain present defines the isotype of antibody;these chains are found in IgA, IgD, IgE, IgG, and IgM antibodies,respectively.

Distinct heavy chains differ in size and composition; α and γ containapproximately 450 amino acids and δ approximately 500 amino acids, whileμ and ε have approximately 550 amino acids. Each heavy chain has tworegions, the constant region (C_(H)) and the variable region (V_(H)). Inone species, the constant region is essentially identical in allantibodies of the same isotype, but differs in antibodies of differentisotypes. Heavy chains γ, α and δ have a constant region composed ofthree tandem Ig domains, and a hinge region for added flexibility; heavychains μ and ε have a constant region composed of four immunoglobulindomains. The variable region of the heavy chain differs in antibodiesproduced by different B cells, but is the same for all antibodiesproduced by a single B cell or B cell clone. The variable region of eachheavy chain is approximately 110 amino acids long and is composed of asingle Ig domain.

In mammals, there are two types of immunoglobulin light chain denoted byλ and κ. A light chain has two successive domains: one constant domain(CL) and one variable domain (VL). The approximate length of a lightchain is 211 to 217 amino acids. Each antibody contains two light chainsthat are always identical; only one type of light chain, κ or λ, ispresent per antibody in mammals.

Although the general structure of all antibodies is very similar, theunique property of a given antibody is determined by the variable (V)regions, as detailed above. More specifically, variable loops, threeeach the light (VL) and three on the heavy (VH) chain, are responsiblefor binding to the antigen, i.e. for its antigen specificity. Theseloops are referred to as the Complementarity Determining Regions (CDRs).Because CDRs from both VH and VL domains contribute to theantigen-binding site, it is the combination of the heavy and the lightchains, and not either alone, that determines the final antigenspecificity.

An “antibody fragment” contains at least one antigen binding fragment asdefined above, and exhibits essentially the same function andspecificity as the complete antibody of which the fragment is derivedfrom. Limited proteolytic digestion with papain cleaves the Ig prototypeinto three fragments. Two identical amino terminal fragments, eachcontaining one entire L chain and about half an H chain, are the antigenbinding fragments (Fab). The third fragment, similar in size butcontaining the carboxyl terminal half of both heavy chains with theirinterchain disulfide bond, is the crystalizable fragment (Fc). The Fccontains carbohydrates, complement-binding, and FcR-binding sites.Limited pepsin digestion yields a single F(ab′)2 fragment containingboth Fab pieces and the hinge region, including the H-H interchaindisulfide bond. F(ab′)2 is divalent for antigen binding. The disulfidebond of F(ab′)2 may be cleaved in order to obtain Fab′. Moreover, thevariable regions of the heavy and light chains can be fused together toform a single chain variable fragment (scFv).

Pharmaceutically acceptable salts are for example acid addition saltsand basic salts. Acid addition salts are e.g. HCl or HBr salts. Basicsalts are e.g. salts having a cation selected from alkali or alkaline,e.g. Na+, or K+, or Ca2+, or an ammonium ion N+(R1)(R2)(R3)(R4), whereinR1 to R4 independently of each other mean: hydrogen, an optionallysubstituted C1-C6-alkyl group, an optionally substituted C2-C6-alkenylgroup, an optionally substituted C6-C10-aryl group, or an optionallysubstituted C6-C10-heteroaryl group. Further examples ofpharmaceutically acceptable salts are described in “Remington'sPharmaceutical Sciences” 17. ed. Alfonso R. Gennaro (Ed.), MarkPublishing Company, Easton, Pa., U.S.A., 1985 and in Encyclopedia ofPharmaceutical Technology.

Pharmaceutically acceptable solvates are for example hydrates.

Those of skill in the art will understand that modifications (additionsand/or removals) of various components of the apparatuses, methodsand/or systems and embodiments described herein may be made withoutdeparting from the full scope and spirit of the present invention, whichencompass such modifications and any and all equivalents thereof.

1-15. (canceled)
 16. An autoinjector comprising: a case; a plungerarranged within the case; a drive spring applying a biasing force to theplunger; and a needle shroud slidably arranged in the case.
 17. Theautoinjector according to claim 16, wherein the case comprises a rearcase, and wherein the needle shroud and the plunger are arranged suchthat a translation of the needle shroud into the case into a proximaldirection results in a rotation that causes release of the plunger fromthe rear case.
 18. The autoinjector according to claim 17, wherein theplunger is adapted to push a stopper in a syringe when moving in adistal direction.
 19. The autoinjector according to claim 17, furthercomprising a control spring that is configured to be compressed by theneedle shroud when the needle shroud moves in the proximal direction.20. The autoinjector according to claim 19, further comprising hooks ona distal end of the needle shroud and a distal case shoulder on thecase.
 21. The autoinjector according to claim 20, wherein the hooks areadapted to engage the distal shoulder to limit extension of the needleshroud relative to the case under a force of the control spring.
 22. Theautoinjector according to claim 21, wherein the hooks extend radiallyoutwards relative to a longitudinal axis of the autoinjector.
 23. Theautoinjector according to claim 22, further comprising resilientnon-return features that are arranged on the needle shroud and that areadapted to engage the case after the needle shroud has been extendedafter an injection.
 24. The autoinjector according to claim 16, whereina translation of the needle shroud causes rotation of the plunger. 25.The autoinjector according to claim 24, wherein the plunger is adaptedto push a stopper in a syringe.
 26. The autoinjector according to claim24, further comprising a control spring that is configured to becompressed by the needle shroud when the needle shroud moves in aproximal direction.
 27. The autoinjector according to claim 26, furthercomprising hooks on a distal end of the needle shroud and a distal caseshoulder on the case.
 28. The autoinjector according to claim 27,wherein the hooks are adapted to engage the distal shoulder to limitextension of the needle shroud relative to the case under a force of thecontrol spring.
 29. The autoinjector according to claim 28, wherein thehooks extend radially outwards relative to a longitudinal axis of theautoinjector.
 30. The autoinjector according to claim 29, furthercomprising resilient non-return features that are arranged on the needleshroud and that are adapted to engage the case after the needle shroudhas been extended after an injection.
 31. The autoinjector according toclaim 16, further comprising a syringe carrier adapted to hold asyringe.
 32. The autoinjector according to claim 31, further comprisingthe syringe.
 33. The autoinjector according to claim 32, wherein thesyringe comprises a needle.
 34. The autoinjector according to claim 32,wherein the syringe comprises a medicament.